Journal of Natural Products 最新文献_第3页

Genome Mining of the Marine-Derived Fungus Trichoderma erinaceum F1-1 Unearths Bergamotene-Type Sesquiterpenoids.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-12-02 DOI: 10.1021/acs.jnatprod.4c00905

Wencong Yang, Shurong Tian, Yi-Fan Du, Xian-Liang Zeng, Jia-Jing Liang, Wen-Jian Lan, Hang Li

{"title":"Genome Mining of the Marine-Derived Fungus Trichoderma erinaceum F1-1 Unearths Bergamotene-Type Sesquiterpenoids.","authors":"Wencong Yang, Shurong Tian, Yi-Fan Du, Xian-Liang Zeng, Jia-Jing Liang, Wen-Jian Lan, Hang Li","doi":"10.1021/acs.jnatprod.4c00905","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00905","url":null,"abstract":"Terpenoids are a vast group of natural products known for their remarkable biological properties and structural diversity. UbiA terpene synthases are increasingly recognized for producing various terpenoids. In this study, we identified a biosynthetic gene cluster (bgt) encoding a UbiA terpene synthase BgtA in the genome of the marine-derived fungus Trichoderma erinaceum F1-1. The gene bgtA was validated to encode the biosynthesis of (-)-α-trans-bergamotene (1). Heterologous expression of the bgt gene cluster in the characterized host Aspergillus nidulans LO8030 activated the biosynthetic pathway, leading to the isolation of eight previously undocumented bergamotene-derived sesquiterpenoids (2-9). Their structures, including the absolute configurations, were elucidated by a combination of spectroscopic analysis, ECD spectra, chemical hydrolysis, single-crystal X-ray diffraction, and biosynthetic considerations. We further demonstrated that the production of these structurally intricate sesquiterpenoids in heterologous expression is attributable to the concerted action of the UbiA terpene synthase BgtA, the cytochrome P450 BgtC, and endogenous enzymes. This study underscores the immense biosynthetic potential of fungal UbiA terpene synthase gene clusters and shows genome mining is a promising strategy for the discovery of novel terpenoids from fungi.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis, Biological Evaluation, and Mechanistic Insights of Rubrolide Analogues as Antitumor Agents. 作为抗肿瘤药物的 Rubrolide 类似物的合成、生物学评价和机理研究。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-28 DOI: 10.1021/acs.jnatprod.4c00946

Haoyu Wu, Guangyao Lv, Liying Liu, Ruilin Hu, Feng Zhao, Mingxiang Song, Sisi Zhang, Huaying Fan, Shengjun Dai, Saif Ur Rehman, Hongbo Wang, Xiaofeng Mou

{"title":"Synthesis, Biological Evaluation, and Mechanistic Insights of Rubrolide Analogues as Antitumor Agents.","authors":"Haoyu Wu, Guangyao Lv, Liying Liu, Ruilin Hu, Feng Zhao, Mingxiang Song, Sisi Zhang, Huaying Fan, Shengjun Dai, Saif Ur Rehman, Hongbo Wang, Xiaofeng Mou","doi":"10.1021/acs.jnatprod.4c00946","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00946","url":null,"abstract":"Marine natural products and their analogues have as of now been acknowledged as an important source of bioactive molecules for the treatment of cancer. Rubrolides, a unique group of γ-butenolides derived from marine microorganisms, have shown strong cytotoxic activity against various tumor cells. In this study, we synthesized and characterized 21 rubrolide analogues (including 16 new compounds) and investigated their antitumor activities in order to screen more active molecules and elucidate their mechanism of action. Primary MTT assay showed that compounds 1 and 4-9 all exhibited excellent antiproliferative activities. In particular, compound 7 showed broad-spectrum cytotoxic activity against six tumor cell lines, with IC50 values mostly ranging from 2.5 to 0.2 μM. Further mechanistic studies revealed that compound 7 could penetrate HCT116 and Hela cells, localize in the endoplasmic reticulum, and upregulate the PERK-eIF2α-CHOP pathway, inducing ER stress and increasing intracellular reactive oxygen species (ROS) levels to ultimately trigger apoptosis in tumor cells. Additionally, compound 7 was found to upregulate Cyclin B1 protein expression, causing cell cycle reticulum at the G2/M phase. In vivo studies further demonstrated that liposomal delivery of compound 7 exhibited a potent antitumor efficacy against Hela xenograft tumors. Based on these results, marine-derived rubrolide analogues show significant potential as novel lead compounds for antitumor drug development.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cyclopeptide Avellanins D-O with Antimalarial Activity from the Mariana Trench Anemone-Derived Hamigera ingelheimensis MSC5. 从马里亚纳海沟天葵提取的 Hamigera ingelheimensis MSC5 中提取的具有抗疟活性的环肽 Avellanins D-O。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-27 DOI: 10.1021/acs.jnatprod.4c00740

Hao Li, Yuling Chen, Bingqing Tang, Zhengjie Liu, Bo Peng, Jiajun Li, Han Gao, Sibao Wang, Zhiyong Li

{"title":"Cyclopeptide Avellanins D-O with Antimalarial Activity from the Mariana Trench Anemone-Derived Hamigera ingelheimensis MSC5.","authors":"Hao Li, Yuling Chen, Bingqing Tang, Zhengjie Liu, Bo Peng, Jiajun Li, Han Gao, Sibao Wang, Zhiyong Li","doi":"10.1021/acs.jnatprod.4c00740","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00740","url":null,"abstract":"Marine microorganisms are a treasure trove of natural products, especially those in extreme marine environments, which may produce novel natural products. Herein, biosynthetic gene cluster analysis combined with an integrated metabolomic strategy incorporating matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), nuclear magnetic resonance (NMR), and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) based Global Natural Products Social Molecular Networking (GNPS) was used to discover new compounds from the Mariana trench anemone-derived fungus Hamigera ingelheimensis MSC5. As a result, 12 new cyclic pentapeptides, avellanins D-O (1-12), were isolated, together with a known cyclic pentapeptide avellanin C (13). All the structures and absolute configurations were elucidated using NMR, mass spectrometry, X-ray diffraction analysis, and Marfey's method. A plausible biosynthetic pathway for the avellanins was proposed based on the gene cluster analysis of H. ingelheimensis MSC5. Bioassay revealed that compound 6 exhibited potent antimalarial activity with an IC50 value of 0.19 ± 0.09 μM.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abietane Diterpenoids from the Rhizomes of Kaempferia roscoeana and Their Anti-Inflammatory Activities. 山奈根茎中的阿比坦二萜及其抗炎活性

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-27 DOI: 10.1021/acs.jnatprod.4c01127

Ratchanaporn Chokchaisiri, Apinya Kaisoda, Sarot Cheenpracha, Lucksagoon Ganranoo, Sareeya Bureekaew, Chutamas Thepmalee, Apichart Suksamrarn

引用次数: 0

Goondomycins A-H: Carbocyclic ansa-Polyketides from an Australian Pasture Streptomyces with Selective Activity against Dirofilaria immitis. Goondomycins A-H: Carbocyclic ansa-Polyketides from an Australian Pasture Streptomyces with Selective Activity against Dirofilaria immitis.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-26 DOI: 10.1021/acs.jnatprod.4c00987

Jianying Han, David F Bruhn, Dana C Roberts, Erica Burkman, Yovany Moreno, Angela A Salim, Robert J Capon

引用次数: 0

Correction to "Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties". 更正 "Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties"。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-25 DOI: 10.1021/acs.jnatprod.4c01221

Jing Guan, Pan Pan Zhang, Xin Hui Wang, Yu Tong Guo, Zi Jin Zhang, Peng Li, Li Ping Lin

引用次数: 0

Goondolinones A and B: Terpenyl-quinolin-4(1H)-ones from an Australian Volcanic Crater Soil-Derived Actinomadura sp., with Selective Activity against Dirofilaria immitis (Heartworm). Goondolinones A and B: Terpenyl-quinolin-4(1H)-ones from an Australian Volcanic Crater Soil-Derived Actinomadura sp.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-24 DOI: 10.1021/acs.jnatprod.4c01146

Jianying Han, David F Bruhn, Dana C Roberts, Erica J Burkman, Yovany Moreno, Paul V Bernhardt, Angela A Salim, Robert J Capon

{"title":"Goondolinones A and B: Terpenyl-quinolin-4(1H)-ones from an Australian Volcanic Crater Soil-Derived Actinomadura sp., with Selective Activity against Dirofilaria immitis (Heartworm).","authors":"Jianying Han, David F Bruhn, Dana C Roberts, Erica J Burkman, Yovany Moreno, Paul V Bernhardt, Angela A Salim, Robert J Capon","doi":"10.1021/acs.jnatprod.4c01146","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01146","url":null,"abstract":"A chemical investigation of the Australian pasture soil-derived Actinomadura sp. S4S-00245B09, supported by chemical, bioactivity and cultivation profiling, yielded a new class of terpenyl-quinolin-4(1H)-ones, goondolinones A and B (1 and 2), featuring an unprecedented fused seven-membered ether. Structures were assigned to 1 and 2 on the basis of detailed spectroscopic analysis, including X-ray analysis of 1, and biosynthetic considerations. Goondolinone A (1) lacks antibacterial or antifungal properties, is noncytotoxic to two human carcinoma cell lines, but exhibits selective inhibition of the motility of heartworm Dirofilaria immitis microfilaria (EC50 5.1 μM) and L4 larvae (EC50 21.4 μM). As a new anthelmintic scaffold, future understanding of the structure activity relationship and mechanism of action of 1 could inform the discovery of new treatments for heartworm and other filarial diseases, capable of safeguarding the health and welfare of companion animals.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Natural Products with Potential for the Treatment of Pain: Global Evidence from the NAPRALERT Database. 具有治疗疼痛潜力的天然产品：来自 NAPRALERT 数据库的全球证据。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-22 Epub Date: 2024-10-29 DOI: 10.1021/acs.jnatprod.4c00439

James G Graham, Jonathan Bisson, Guy H Harris, Zaijie Jim Wang, Donald P Waller, Guido F Pauli

{"title":"Natural Products with Potential for the Treatment of Pain: Global Evidence from the NAPRALERT Database.","authors":"James G Graham, Jonathan Bisson, Guy H Harris, Zaijie Jim Wang, Donald P Waller, Guido F Pauli","doi":"10.1021/acs.jnatprod.4c00439","DOIUrl":"10.1021/acs.jnatprod.4c00439","url":null,"abstract":"Natural products (NPs) continue to inform the discovery and development of a diversity of drugs, both marketed and investigational. Pain, one of the most common of human experiences and profound challenges in medicine and biology, has emerged at the core of an urgent societal problem, in the United States and globally. The present study employs a retrospective analysis of an extensive set of published literature curated in the NAPRALERT database to identify NPs with experimental evidence of bioactivity supporting the selection and prioritization of NP leads with promise in pain management. The NAPRALERT pain data set currently documents >38,000 pain-relevant experiments reported in >1,750 distinct journals. The evidence presented here was annotated from >10,000 distinct scientific publications identifying NP extracts and isolates with experimental biological data indicating positive mitigation of pain, inflammation, and/or modulation of nociceptive signaling targets. Correlation of ethnomedical uses with experimental data represents a value-added approach to the selection and prioritization of leads. Dissemination of this unique NP/pain data set, with experimental data and information applicable to basic, translational, and clinical science stakeholders alike, furnishes practical evidence in support of a rational selection of NPs for directed pain research. A large portion of the NAPRALERT pain-relevant data set, along with a set of query tools designed to assist user-directed selection and prioritization of leads, are presented as Supporting Information in order to mitigate the limitations inherent in presenting such a large data set in (print) format. To support user efforts, this report involves explication of NAPRALERT data organization and the articulation of rational approaches to user-guided selection of evidence-based NP leads.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2665-2675"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Biological Targets of Magnolol and Honokiol and their Nature-Inspired Synthetic Derivatives: In Silico Identification and Experimental Validation of Estrogen Receptors. 探索 Magnolol 和 Honokiol 及其自然启发合成衍生物的生物靶标：雌激素受体的硅学鉴定和实验验证。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-22 Epub Date: 2024-11-11 DOI: 10.1021/acs.jnatprod.4c00634

Annachiara Tinivella, Jerome C Nwachukwu, Luca Pinzi, Maria Antonietta Dettori, Davide Fabbri, Paola Carta, Kendall W Nettles, Giulio Rastelli

{"title":"Exploring Biological Targets of Magnolol and Honokiol and their Nature-Inspired Synthetic Derivatives: In Silico Identification and Experimental Validation of Estrogen Receptors.","authors":"Annachiara Tinivella, Jerome C Nwachukwu, Luca Pinzi, Maria Antonietta Dettori, Davide Fabbri, Paola Carta, Kendall W Nettles, Giulio Rastelli","doi":"10.1021/acs.jnatprod.4c00634","DOIUrl":"10.1021/acs.jnatprod.4c00634","url":null,"abstract":"In this work, we describe the results of a computational investigation aimed at identifying potential biological targets of honokiol, magnolol and a series of synthetic prodrug derivatives obtained through esterification of the free hydroxyl groups. The ligand-based and structure-based analyses revealed that these compounds potentially interact with several biological targets, some of which are known while others are new. Honokiol, magnolol, and three of the newly synthesized derivatives may bind to estrogen receptors ERα and ERβ. Biological testing confirmed that these compounds modulate estrogen-regulated transcriptional activity mediated by ERα or ERβ with potencies in the nanomolar range. In particular, magnolol and one of its derivatives (10) behaved as partial antagonists of ERα and ERβ, while compounds 8 and 11 behaved as partial agonists. These findings validate the computational predictions and shed light on the mechanism of action of these natural compounds, paving the way for further investigation in the context of targeted therapies.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2568-2579"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Divergent Total Synthesis of Isoflavone Natural Products and Their Potential as Therapeutic Agents for TTR Amyloidosis. 异黄酮天然产品的不同全合成及其作为 TTR 淀粉样变性治疗剂的潜力。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-11-22 Epub Date: 2024-10-27 DOI: 10.1021/acs.jnatprod.4c00812

Nguyen Ngoc Thanh Luan, Takuya Okada, Takeshi Yokoyama, Mie Suzuki, Yuko Nabeshima, Mineyuki Mizuguchi, Naoki Toyooka

引用次数: 0